To the Editor.
—1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes parkinsonism in humans and experimental animals by causing the death of dopaminergic striatal neurons. The ultimate toxin is thought to be a monoamine oxidase metabolite of MPTP, the 1-methyl-4-phenylpyridinium ion (MPP+), which is transported by the normal dopamine reuptake system, is concentrated by the mitochondria, and then poisons the cell by blocking the respiratory chain.1-3Several authors have presented evidence for the involvement of oxygen radical damage in the toxic effects of MPTP.4 Dopaminergic neurons accumulate lipofuscin, a hallmark of oxidative damage, after MPTP administration.5,6 Some experiments, although not all, have demonstrated amelioration of MPTP-caused dopaminergic neuron loss by prior administration of antioxidants, including vitamin E.2,7 Other data also demonstrate initiation of oxidative damage by MPTP in various systems.8-10 Moreover, the possible involvement of oxidative damage in the loss of dopaminergic neurons in idiopathic Parkinson's disease has led to
Hornsby PJ. Parkinson's Disease, Vitamin E, and Mitochondrial Energy Metabolism. Arch Neurol. 1989;46(8):840–841. doi:10.1001/archneur.1989.00520440020007
Customize your JAMA Network experience by selecting one or more topics from the list below.